Transcription of <i>HOX</i> Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease
Parkinson’s disease (PD) is the most serious movement disorder, but the actual cause of this disease is still unknown. Induced pluripotent stem cell-derived neural cultures from PD patients carry the potential for experimental modeling of underlying molecular events. We analyzed the RNA-seq data of...
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MDPI AG
2023-05-01
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| Series: | Journal of Developmental Biology |
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| Online Access: | https://www.mdpi.com/2221-3759/11/2/23 |
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| author | Viya B. Fedoseyeva Ekaterina V. Novosadova Valentina V. Nenasheva Lyudmila V. Novosadova Igor A. Grivennikov Vyacheslav Z. Tarantul |
| author_facet | Viya B. Fedoseyeva Ekaterina V. Novosadova Valentina V. Nenasheva Lyudmila V. Novosadova Igor A. Grivennikov Vyacheslav Z. Tarantul |
| author_sort | Viya B. Fedoseyeva |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is the most serious movement disorder, but the actual cause of this disease is still unknown. Induced pluripotent stem cell-derived neural cultures from PD patients carry the potential for experimental modeling of underlying molecular events. We analyzed the RNA-seq data of iPSC-derived neural precursor cells (NPCs) and terminally differentiated neurons (TDNs) from healthy donors (HD) and PD patients with mutations in <i>PARK2</i> published previously. The high level of transcription of <i>HOX</i> family protein-coding genes and lncRNA transcribed from the <i>HOX</i> clusters was revealed in the neural cultures from PD patients, while in HD NPCs and TDNs, the majority of these genes were not expressed or slightly transcribed. The results of this analysis were generally confirmed by qPCR. The <i>HOX</i> paralogs in the 3′ clusters were activated more strongly than the genes of the 5′ cluster. The abnormal activation of the <i>HOX</i> gene program upon neuronal differentiation in the cells of PD patients raises the possibility that the abnormal expression of these key regulators of neuronal development impacts PD pathology. Further research is needed to investigate this hypothesis. |
| first_indexed | 2024-03-11T02:18:13Z |
| format | Article |
| id | doaj.art-44ad197f5bfe4d43aca0e6972293d344 |
| institution | Directory Open Access Journal |
| issn | 2221-3759 |
| language | English |
| last_indexed | 2024-03-11T02:18:13Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Developmental Biology |
| spelling | doaj.art-44ad197f5bfe4d43aca0e6972293d3442023-11-18T11:02:55ZengMDPI AGJournal of Developmental Biology2221-37592023-05-011122310.3390/jdb11020023Transcription of <i>HOX</i> Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s DiseaseViya B. Fedoseyeva0Ekaterina V. Novosadova1Valentina V. Nenasheva2Lyudmila V. Novosadova3Igor A. Grivennikov4Vyacheslav Z. Tarantul5Institute of Molecular Genetics of National Research Centre “Kurchatov Institute”, Moscow 123182, RussiaInstitute of Molecular Genetics of National Research Centre “Kurchatov Institute”, Moscow 123182, RussiaInstitute of Molecular Genetics of National Research Centre “Kurchatov Institute”, Moscow 123182, RussiaInstitute of Molecular Genetics of National Research Centre “Kurchatov Institute”, Moscow 123182, RussiaInstitute of Molecular Genetics of National Research Centre “Kurchatov Institute”, Moscow 123182, RussiaInstitute of Molecular Genetics of National Research Centre “Kurchatov Institute”, Moscow 123182, RussiaParkinson’s disease (PD) is the most serious movement disorder, but the actual cause of this disease is still unknown. Induced pluripotent stem cell-derived neural cultures from PD patients carry the potential for experimental modeling of underlying molecular events. We analyzed the RNA-seq data of iPSC-derived neural precursor cells (NPCs) and terminally differentiated neurons (TDNs) from healthy donors (HD) and PD patients with mutations in <i>PARK2</i> published previously. The high level of transcription of <i>HOX</i> family protein-coding genes and lncRNA transcribed from the <i>HOX</i> clusters was revealed in the neural cultures from PD patients, while in HD NPCs and TDNs, the majority of these genes were not expressed or slightly transcribed. The results of this analysis were generally confirmed by qPCR. The <i>HOX</i> paralogs in the 3′ clusters were activated more strongly than the genes of the 5′ cluster. The abnormal activation of the <i>HOX</i> gene program upon neuronal differentiation in the cells of PD patients raises the possibility that the abnormal expression of these key regulators of neuronal development impacts PD pathology. Further research is needed to investigate this hypothesis.https://www.mdpi.com/2221-3759/11/2/23Parkinson’s diseaseinduced pluripotent stem cellsneural precursor cellsterminally differentiated neuronsRNA-seq<i>HOX</i> genes |
| spellingShingle | Viya B. Fedoseyeva Ekaterina V. Novosadova Valentina V. Nenasheva Lyudmila V. Novosadova Igor A. Grivennikov Vyacheslav Z. Tarantul Transcription of <i>HOX</i> Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease Journal of Developmental Biology Parkinson’s disease induced pluripotent stem cells neural precursor cells terminally differentiated neurons RNA-seq <i>HOX</i> genes |
| title | Transcription of <i>HOX</i> Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease |
| title_full | Transcription of <i>HOX</i> Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease |
| title_fullStr | Transcription of <i>HOX</i> Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease |
| title_full_unstemmed | Transcription of <i>HOX</i> Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease |
| title_short | Transcription of <i>HOX</i> Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease |
| title_sort | transcription of i hox i genes is significantly increased during neuronal differentiation of ipscs derived from patients with parkinson s disease |
| topic | Parkinson’s disease induced pluripotent stem cells neural precursor cells terminally differentiated neurons RNA-seq <i>HOX</i> genes |
| url | https://www.mdpi.com/2221-3759/11/2/23 |
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